CELL INTELLIGENCE · 肿瘤细胞治疗研究

Breast cancer is the most common and deadliest cancer in women worldwide. Among the distinct subtypes, triple negative breast cancer (TNBC) stands out as the most aggressive one, showing high resistance to treatments, including chemotherapy, radiotherapy, and immunotherapy. Radiotherapy remains a standard treatment for TNBC, offering significant benefits in reducing local relapse. However, resistance to radiotherapy remains a major challenge, limiting its effectiveness and narrowing treatment options. Radioresistance in TNBC is driven by both tumor cell-intrinsic mechanisms and tumor immune microenvironment (TIME)-related processes. Intrinsically, TNBC cells employ strategies such as enhanced DNA damage repair mechanisms, tumor hypoxia adaptation, activation of survival pathways, and the contribution of cancer stem cells and extracellular vesicles. Extrinsically, the TIME can further fuel resistance by recruiting immunosuppressive cells (myeloid-derived suppressor cells, macrophages, neutrophils and regulatory T cells) and by releasing factors that impair the antitumor immune response mediated by T cells and natural killer cells. This review explores the dual contribution of cancer cell-specific mechanisms and TIME dynamics in TNBC radioresistance. We further discuss the paradoxical role of the immune system in radioresponse, highlighting emerging combination therapies, and address the challenges of translating these strategies into clinical applications. Ongoing clinical trials targeting radioresistance are also summarized, reflecting the latest efforts to enhance therapeutic outcomes for TNBC patients.